Regulated glycosylation patterns of IgG during alloimmune responses against human platelet antigens.
Various biological activities of immunoglobulin G (IgG) including antibody-dependent cellular cytotoxicity (ADCC) are modulated by the structural features of the N-glycans in the Fc part. In this study, we describe a population of IgG1 alloantibodies which are formed during pregnancy against human platelet antigens (HPA) of the fetus, causing fetoneonatal alloimmune thrombocytopenia. By analyzing the Fc-glycosylation of the pathogenic, affinity-purified IgG1 alloantibodies at the glycopeptide level using mass spectrometry, we found markedly decreased levels of core-fucosylation as well as increased levels of galactosylation and sialylation as compared to glycosylation patterns of total serum IgG1 of the same patients. Because IgG1 Fc-core-fucosylation is known to influence ADCC activity, modulation of core-fucosylation may have a profound effect on disease severity and prognosis. Studies in large patient cohorts will have to be performed to establish such correlations. Moreover, experiments in animal models as well as in vitro immunological tests will be needed to unravel the mechanisms regulating IgG Fc glycosylation.
Wuhrer
Manfred
M
Department of Parasitology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. m.wuhrer
Porcelijn
Leendert
L
Kapur
Rick
R
Koeleman
Carolien A M
CA
Deelder
André
A
de Haas
Masja
M
Vidarsson
Gestur
G
D000328:Adult; D000368:Aged; D016824:Antigens, Human Platelet / Q000737:chemistry / Q000276:immunology; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D005260:Female; D006031:Glycosylation; D006801:Humans; D007107:Immune System / Q000276:immunology*; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology; D007155:Immunologic Factors / Q000737:chemistry / Q000276:immunology; D007518:Isoantibodies / Q000737:chemistry / Q000276:immunology; D008875:Middle Aged; D008969:Molecular Sequence Data; D011247:Pregnancy
D016824:Antigens, Human Platelet; D007074:Immunoglobulin G; D007155:Immunologic Factors; D007518:Isoantibodies